title: How to avoid being surprised by hepatotoxicity at the final stages of drug development and approval.
abstract: Drugs that caused severe drug-induced live injury (DILI) in humans have typically not shown clear hepatotoxic signals in preclinical assessment. However, clinical trial databases may show evidence of a drug's potential for severe DILI if clinical and laboratory data are evaluated for evidence of milder liver injury. The most specific indicator during a clinical trial for a drug's potential to cause severe DILI is occurrence of cases of drug induced hepatocellular injury accompanied by altered liver function (eg, elevated direct bilirubin). Meticulous causality assessment of hepatic cases and strict adherence to hepatic discontinuation rules are critical components of this approach.
authors.affiliation: Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center, Indiana University School of Medicine, Drop Code 2121, Indianapolis, IN 46285, USA. Electronic address: regev_arie@lilly.com.
authors.forename: Arie
authors.initials: A
authors.lastname: Regev
mesh_terms: D054316:Biomarkers, Pharmacological / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000209:etiology* / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D006801:Humans
chemical_list: D054316:Biomarkers, Pharmacological
keywords: Causality assessment; Drug development; Drug-induced liver injury; Hy’s Law